Abstract
Immunostimulants and vaccines are important for controlling infectious diseases in fish aquaculture. In this study we assess the potential of flagellin to be used for such purposes in rainbow trout (Oncorhynchus mykiss). A recombinant flagellin from the salmonid pathogen Yersinia ruckeri (YRF) has been produced previously by us and shown to be a potent activator of inflammatory cytokines, acute phase proteins and antimicrobial peptides in vitro. Here we show that YRF is the most potent inflammatory activator of three bacterial PAMPs (LPS, peptidoglycan and flagellin) tested. The host response to flagellin was next studied in vivo. The YRF modulated gene expression was examined in two systemic (spleen and liver) and two mucosa-associated (gills and skin) tissues. YRF injection initiated a transient systemic inflammatory response with key pro-inflammatory cytokines (IL-1β, TNFα, IL-6, and IL-11 etc.) and chemokines (CXCL_F4 and CXCL-8) induced rapidly (by 6 h) but subsiding quickly (by 24 h) in multiple tissues. Consequently, a variety of anti-microbial pathways were activated systemically with heightened expression of acute phase proteins, antimicrobial peptides and complement genes in multiple tissues, which was sustained to 24 h in the liver and mucosal tissues. The Th17 cytokine IL-17A/F1 was also induced in the spleen and liver, and Th2 cytokine IL-4/13 was induced in the liver. However, the anti-inflammatory IL-10 and the Th1 cytokine IFNγ were refractory. A secreted form of TLR5 (TLR5s) was induced by flagellin in all tissues examined whilst the membrane form was refractory, suggesting that TLR5s may function as a negative feedback regulator. Trout liver appeared to be an important organ responding to flagellin stimulation, with marked induction of IL-11, IL-23P19, IL-17C1, SAA, and cathelicidin-2. YRF induced a strong antibody response. These antibodies reacted against the middle domain of YRF and were able to decrease YRF bioactivity. Intact YRF was necessary for its bioactivity, as deletion of the N-terminal, C terminal or middle domain of YRF led to functional loss. This study suggests that flagellin could be a potent immunostimulant and vaccine adjuvant for fish aquaculture.
| Original language | English |
|---|---|
| Article number | 3054 |
| Journal | Frontiers in Immunology |
| Volume | 9 |
| DOIs | |
| Publication status | Published - 9 Jan 2019 |
Bibliographical note
EW was supported by a Ph.D. studentship from the Ministry of Science and Technology of Thailand and Mahasarakham University. TW received funding from the MASTS pooling initiative (The Marine Alliance for Science and Technology for Scotland), that is funded by the Scottish Funding Council (grant reference HR09011). This research was also funded by the European Commission under the 7th Framework Programme for Research and Technological Development (FP7) of the European Union (grant agreement No. 311993 TARGETFISH).The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fimmu.2018.03054/full#supplementary-material
Keywords
- flagellin
- Immunostimulant
- vaccine adjuvant
- salmonids
- cytokine
- antimicrobial peptides
- gene expression
- inflammatory response
- Vaccine adjuvant
- Cytokine
- Flagellin
- Inflammatory response
- Gene expression
- Antimicrobial peptides
- Salmonids
- IMMUNE-RESPONSE
- immunostimulant
- EXPRESSION ANALYSIS
- BACTERIAL FLAGELLIN
- EDWARDSIELLA-TARDA
- TROUT ONCORHYNCHUS-MYKISS
- ATLANTIC SALMON
- DIFFERENTIAL EXPRESSION
- FUNCTIONAL-CHARACTERIZATION
- RECEPTOR 5
- CYTOKINE FAMILY
Access to Document
- Studies on the Use of Flagellin as an Immunostimulant and Vaccine Adjuvant in Fish Aquaculture
Copyright © 2019 Wangkahart, Secombes and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. https://creativecommons.org/licenses/by/4.0/